title: Adjuvant treatment for resected renal cell carcinoma: are all strategies equally negative? Potential implications for trial design with targeted agents.
abstract: BACKGROUND
  Although data from ongoing trials with targeted agents are awaited, we used a meta-analytical approach to explore whether cytokines (CK), vaccines (VAX), or other therapies may differentially influence patients' outcomes.
  
  
  METHODS
  The objective was to determine whether significant interactions exist according to treatment (CK vs. VAX vs. other), in the context of a literature-based meta-analysis. Fourteen trials (3380 patients) were identified, with 10 randomized clinical trials (RCTs) (2257 patients) providing data for the primary outcome--5-year relapse-free survival (RFS). The primary selected end point was 5-year RFS; secondary end points were 5- and 2-year overall survival (OS) and 2-year RFS. Event-based relative risk (RR) ratios with 95% confidence intervals (CI) were extracted and cumulated according to a random-effect model from articles/presentations. Testing for heterogeneity was performed as well.
  
  
  RESULTS
  Although not statistically significant, an effect in favor of a qualitative interaction according to treatment was found for 5-year RFS, with a likely detrimental effect in CK (P = .42) in contrast to that found in VAX subpopulation (P = .76). For the secondary end points, a similar effect in favor of a quantitative significant interaction according to treatment was found for 5-year OS, regardless of the approach adopted, with a different magnitude of treatment effect. In addition, a borderline significant (P = .05) detrimental effect in terms of 2-year OS against the use of adjuvant treatment was determined in the CK subpopulation (RR, 1.24; 95% CI, 0.99, 1.54).
  
  
  CONCLUSIONS
  The effect in favor of a qualitative interaction according to the adopted strategy is intriguing and suggests potential implications for trial design with targeted agents.
authors.affiliation: Department of Medical Oncology, "G.B. Rossi" Academic Hospital, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Francesca
authors.initials: F
authors.lastname: Maines
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pappagallo
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000601:surgery; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D009364:Neoplasm Recurrence, Local; D013534:Survival
keywords: Adjuvant; Interaction; Meta-analysis; Renal cell carcinoma